I have developed a mammalian mitochondria (mt) genetics system based on resistance to chloramphenicol (CAP). This mutation was shown to be cytoplasmically inherited by removing the nucleus of resistant (R) cells and fusing the cytoplasmic fragments to sensitive (S) cells (cybrid formation). Subsequent studies have demonstrated that CAP resistance is coded on the mtDNA, that there are mt incompatibility relationships between different cell lines, that mtDNA can be fixed in cells of different species, and that the nuclear coded mt genes are dispersed throughout the chromosomes. Recent evidence suggests that the RNA tumor viruses may use the mitochondria both for provirus synthesis and for virion synthesis and assembly. To test this association, I propose to subdivide virally-infected CAP-R cells and transfer the various fragments to uninfected CAP-S cells. Examination of co-transfer of the virus and CAP resistance should permit intracellular location of the viral genome. Since both the mitochondria and the RNA tumor viruses seem to regulate nuclear DNA (nDNA) synthesis as well as the genes necessary for their synthesis, it is possible that they might use the same or similar mechanisms for nuclear control. Mt genetic studies will be extended with particular attention to their relationship to RNA tumor virus cellular reglation and host range. Studies on the number of mt compatibility types will be expanded and the mechanisms of compatibility explored. These data will be related to parallel observations made on murine leukemia virus host cell specificity. Further studies on the arrangement of mt genes on the mtDNA and nDNA will employ interspecific cybrids and mapping of additional mt mutants. These data, in conjunction with studies on the mechanisms of mt control of the nucleus, may result in further insight into RNA tumor virus regulation of the cell. Finally, mouse teratocarcinoma cells containing foreign CAP-R mitochondria will be monitored as they are brought under growth control in developing embryos. These experiments will provide data on the role of the mitochondria in maintenance of the transformed state and could result in the generation of CAP-R mice which would be used in the study of inheritance of mt genes during meiosis.